Description: This proposed research seeks to understand how virus and host control innate immune defenses and the outcome of WNV infection. WNV is described as a model flavivirus which is representative of other members of the family. The PL has defined specific PRR pathways and IRFs as key to immune triggering and programming during WNV infection. It is hypothesized that viral triggering and control of PRR and signaling programs and innate immune defenses of the host cell defines the tissue tropism and virulence properties of WNV infection. The PL proposes to conduct in vitro and in vivo studies to 1) define cell specific PRR pathways that trigger innate immunity against WNV 2) Identify the IFN stimulated innate immune effector genes that control WNV replication and 3) determine the molecular mechanism by which pathogenic WNV evades the innate immune actions of IFN?/?.